Tag Archives: CB(1) and CB(2) receptors

Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

Posted on by
Reply

“Cannabinoids inhibit skin tumor growth in vivo. Here we show that the CB1 and the CB2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB1/CB2 agonist WIN-55,212-2 or the selective CB2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells.

 

Cannabinoids, the active components of Cannabis sativa linnaeus (marijuana)…

Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renaissance in the study of the therapeutic effects of cannabinoids… cannabinoids may be potential antitumoral agents owing to their ability to induce the regression of various types of tumors, including lung adenocarcinoma, glioma, and thyroid epithelioma in animal models.

This background prompted us to explore whether (a) the skin and skin tumors express cannabinoid receptors; (b) cannabinoid receptor activation exerts a growth-inhibiting action on skin tumors in vivo; and (c) inhibition of angiogenesis is implicated in the anti-tumoral effect of cannabinoids.

Our data show that (a) CB1 and CB2 receptors are present in the skin and skin tumors; (b) local cannabinoid receptor activation induces the regression of skin tumors in vivo; and (c) at least two mechanisms may be involved in this action: direct apoptosis of tumor cells and inhibition of tumor angiogenesis.

These results support a new therapeutic approach for the treatment of skin tumors.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151833/

The Cannabinoid Receptors are Required for UV-Induced Inflammation and Skin Cancer Development

Posted on by
Reply

“Solar ultraviolet (UV) irradiation is an important carcinogen that leads to the development of skin cancer, which is the most common human cancer. However, the receptors that mediate UV-induced skin carcinogenesis have not yet been unequivocally identified. Here we showed that UV irradiation directly activates the cannabinoid receptors 1 and 2 (CB1/2)…

These data provide direct evidence indicating that the CB1/2 receptors play a key role in UV-induced inflammation and skin cancer development…

Manipulation of the cannabinoid receptors has been useful in the management of pain, treatment of osteoporosis, inflammation, and cancer…”

.Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390870/

 

Peripheral Cannabinoids Attenuate Carcinoma Induced Nociception in Mice

Posted on by
Reply

“Cancer pain remains poorly understood and there are no effective therapies…

 We tested whether a local CBr2 agonist produces antinociception. Our findings suggest that a peripheral CBr2 agonist could provide relief for cancer patients. Cannabinoids also potentiate the analgesic effects of morphine and prevent tolerance.

These desirable effects of cannabinoids show promise for management of cancer pain and may lead to improved analgesic therapy.

These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771220/

The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.

Posted on by
Reply

“Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors.

While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin.

 Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/21807457

The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi’s sarcoma cells in vitro.

Posted on by
Reply

“Kaposi’s sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi’s sarcoma cell proliferation in vitro.

 To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi’s sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi’s sarcoma cells…

  In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi’s sarcoma”

http://www.ncbi.nlm.nih.gov/pubmed/19539619

Presence of functional cannabinoid receptors in human endocrine pancreas.

Posted on by
Reply

“We examined the presence of functional cannabinoid receptors 1 and 2 (CB1, CB2) in isolated human islets, phenotyped the cells producing cannabinoid receptors and analysed the actions of selective cannabinoid receptor agonists on insulin, glucagon and somatostatin secretion in vitro. We also described the localisation on islet cells of: (1) the endocannabinoid-producing enzymes N-acyl-phosphatidyl ethanolamine-hydrolysing phospholipase D and diacylglycerol lipase; and (2) the endocannabinoid-degrading enzymes fatty acid amidohydrolase and monoacyl glycerol lipase.

RESULTS:

Human islets of Langerhans expressed CB1 and CB2 (also known as CNR1 and CNR2) mRNA and CB1 and CB2 proteins, and also the machinery involved in synthesis and degradation of 2-AG (the most abundant endocannabinoid, levels of which were modulated by glucose). Immunofluorescence revealed that CB1 was densely located in glucagon-secreting alpha cells and less so in insulin-secreting beta cells. CB2 was densely present in somatostatin-secreting delta cells, but absent in alpha and beta cells. In vitro experiments revealed that CB1 stimulation enhanced insulin and glucagon secretion, while CB2 agonism lowered glucose-dependent insulin secretion, showing these cannabinoid receptors to be functional.

CONCLUSIONS/INTERPRETATION:

Together, these results suggest a role for endogenous endocannabinoid signalling in regulation of endocrine secretion in the human pancreas.”

http://www.ncbi.nlm.nih.gov/pubmed/18092149

Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells.

Posted on by
Reply

“In RIN m5F rat insulinoma beta-cells, agonists at cannabinoid CB(1) receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB(1) and CB(2) receptors on intracellular Ca(2+) ([Ca(2+)](i)). The CB(1) agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB(2) agonist JWH133, elevated [Ca(2+)](i) in a way sensitive to the inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), U73122 (but not to pertussis toxin and forskolin), and independently from extracellular Ca(2+). PI-PLC-dependent Ca(2+) mobilization by ACEA was entirely accounted for by activation of inositol-1,3,4-phosphate (IP(3)) receptors on the endoplasmic reticulum (ER), whereas the effect of JWH133 was not sensitive to all tested inhibitors of IP(3) and ryanodine receptors. ACEA, but not JWH133, significantly inhibited the effect on [Ca(2+)](i) of bombesin, which acts via G(q/11)- and PI-PLC-coupled receptors in insulinoma cells. The endogenous CB(1) agonists, anandamide and N-arachidonoyldopamine, which also activate transient receptor potential vanilloid type 1 (TRPV1) receptors expressed in RIN m5F cells, elevated [Ca(2+)](i) in the presence of extracellular Ca(2+) in a way sensitive to both CB(1) and TRPV1 antagonists. These results suggest that, in RIN m5F cells, CB(1) receptors are coupled to PI-PLC-mediated mobilization of [Ca(2+)](i) and might inhibit bombesin signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/17585904

Effects of CP 55,940–agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas.

Posted on by
Reply

“Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets.”

http://www.ncbi.nlm.nih.gov/pubmed/22532145

The endocannabinoid system and the treatment of mood and anxiety disorders.

Posted on by
Reply

“The central endocannabinoid system is a neuroactive lipid signalling system in the brain which acts to control neurotransmitter release. The expression patterns of this system throughout limbic regions of the brain ideally situate it to exert regulatory control over emotional behaviour, mood and stress responsivity. A growing body of evidence unequivocally demonstrates that deficits in endocannabinoid signalling may result in depressive and anxiogenic behavioral responses, while pharmacological augmentation of endocannabinoid signalling can produce both antidepressive and anxiolytic behavioral responses. The aim of this review is to summarize current knowledge of the role of the endocannabinoid system in the etiology and treatment of mood and anxiety disorders, such as depression, anxiety and post-traumatic stress disorder.

Collectively, both clinical and preclinical data argue that cannabinoid receptor signalling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/19839936

The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives.

Posted on by
Reply

“Alterations in emotion regulation processes may form the basis of psychopathologies. The endocannabinoid (eCB) system, composed of endogenous ligands, the enzymatic machinery in charge of their metabolism and the specific metabotropic receptors, has emerged as a major neuromodulatory system critically involved in the control of emotional homeostasis and stress responsiveness. Data from animal models indicate that the eCB system plays a key role in brain development, and is probably involved in the control of emotional states from early developmental stages.

The present review summarizes the latest information on the role of the eCB system in emotionality and anxiety-related disorders throughout the lifespan. Putative therapeutic strategies based on the pharmacological modulation of this system will be discussed.

 Given the fact that the pharmacological modulation of the eCB system has recently arisen as a promising strategy in the management of anxiety and mood disorders, the potential efficacy of this pharmacological approach (i.e. blockers of the catabolic pathway) will be discussed, as well as pharmacological alternatives such as modulators of cannabinoid receptors other than the classical CB1 receptor, or administration of other plant-derived compounds (e.g. cannabidiol).”

http://www.ncbi.nlm.nih.gov/pubmed/21693551